ABCMdb

PMID: 18029147

Drera B, Brezzi A, Zoppi N, Venturini M, Barlati S, Pinton PG, Colombi M
Compound heterozygosity for a novel and a recurrent ABCC6 gene mutation in an Italian family with Pseudoxanthoma elasticum.
J Dermatol Sci. 2008 Mar;49(3):252-5. Epub 2007 Oct 29., [PubMed]

Sentences

No. Mutations Sentence Comment

11 ABCC6 p.Arg1141* In particular, the p.R1141X mutation represents about 28% of the mutations detected in the European patients and about 26% in Italian ones [1,6]. Login to comment 22 ABCC6 p.Arg1141* ABCC6 p.Gly1133Cys Sequencing analysis of proband`s genomic DNA, disclosed in exon 24 of ABCC6 gene the c.3397G>T transversion and the c.3421C>T transition, leading to p.G1133C missense and p.R1141X nonsense mutations, respectively (Fig. 2A). Login to comment 28 ABCC6 p.Arg1141* ABCC6 p.Gly1133Cys The specific amplification of both alleles, using a wild type and a mutated forward primer at nucleotide c.3397, and the sequence analysis of the PCR products showed that the p.G1133C substitution was in trans with the p.R1141X nonsense mutation (Fig. 2B). Login to comment 29 ABCC6 p.Gly1133Cys Furthermore, the p.G1133C missense mutation was not detected in 200 chromosomes from control Italian donors. Login to comment 31 ABCC6 p.Gly1133Cys Bioinformatic analysis of the p.G1133C functional effects by PolyPhen tool (available online at http://genetics.bwh.harvard.edu/ pph/) predicted that this mutation is damaging Letter to the Editor 253 Fig. 1 PXE patient family pedigree (A) and clinical findings in the proband (B). Login to comment 34 ABCC6 p.Gly1133Cys For all these reasons, the p.G1133C substitution is a novel disease causing mutation. Login to comment 35 ABCC6 p.Gly1133Ala Very recently, the substitution of the p.1133 glycine residue with an alanine (p.G1133A) was reported [7], underlining the importance of this amino acid in MRP6 function maintenance. Login to comment 37 ABCC6 p.Arg1141* The recurrent p.R1141X nonsense mutation has been shown to result in a null allele due to the nonsense-mediated decay of the aberrant mRNA [9]. Login to comment 41 ABCC6 p.Arg1141* Previously, the p.R1141X mutation was reported to be associated with an increased risk of premature, i.e. under the 50 years, coronary artery disease in patients without PXE signs [10]. Login to comment 43 ABCC6 p.Arg1141* In the members of our family carrying the p.R1141X, indeed, cardiovascular involvement, i.e. hypertension, premature coronary artery disease, ischemic stroke or mucosal bleeding, was absent. Login to comment 46 ABCC6 p.Arg1141* ABCC6 p.Gly1133Cys In conclusion, we reported a new Italian PXE family showing intra-familiar variability in the onset and in the systems involvement, in which the disease was due to compound heterozygosity for the novel p.G1133C and the recurrent p.R1141X mutations. Login to comment